Role of extracellular proteins in the dynamics of vasogenic brain edema

Abstract

The relationship between extravasation of proteins into extracellular spaces of brain parenchyma and the water content of such regions were evaluated in an experimental model. In this model, a temporary opening of the blood-brain barrier (BBB) to proteins was produced without significant injury to the cellular elements of brain tissue. Rabbits were subjected to bolus injection of their own blood under 360-400 mm Hg pressure via the internal carotid artery. The opening of the barrier and its duration were evaluated with Evans blue (EB), horseradish peroxidase (HRP), and sodium fluorescein (NaFl) tracers. The water content of brain tissue was assessed by specific gravity (SG) measurements in 1-mm-diameter tissue samples. Quantitative evaluation of protein penetration into brain tissue was carried out using 125I bovine serum albumin (BSA). The opening of the BBB to proteins persisted up to 9 h, whereas the barrier remained permeable to small molecular NaFl for 24 h. The SG measurements indicated in the areas of EB extravasation a progressive increment in water content up to 9 h, i.e., the duration of BBB opening to proteins. Following this, there was a progressive clearance of edema in spite of the BBB remaining open for NaFl for 24 h. Quantitative evaluations of 125I-BSA and SG in the same tissue samples, supported by statistical analysis, indicated approximately linear relationship analysis, indicated approximately linear relationship between albumin and water, implying a strong correlation between the development of vasogenic edema and extravasation of proteins into extracellular spaces.

Cerebrovascular Regulation During Transient Hypotension and Hypertension in Humans

“…25,30,31 Although there is evidence that raised intravascular pressure may compromise the integrity of the blood-brain barrier resulting in "leak through" of intravascular catecholamines, the evidence for this is based on animals studies conducted under conditions that are vastly different from those of the current study, that is, prolonged (hours) periods of extreme hypertension (eg, MAP Ͼ180 mm Hg). 32,33 We acknowledge that new developments in functional MRI will likely provide invaluable insight into how asymmetrical dCA may influence CBF to discreet regions of the brain.…”

Acute Leakage Patterns of Fluorescent Plasma Flow Markers after Transient Focal Cerebral Ischemia Suggest Large Openings in Blood‐Brain Barrier

“…Development and resolution of brain edema after stroke has also been shown to parallel the extravasation of plasma-borne proteins [19]; these authors reported that the injured BBB remained open for plasma albumin for about 9 hr after ischemia and brain water accumulation during this period was observed. These reports of increased striatal susceptibility to microvascular damage and edema are in agreement with the present results of striatal hyperemia, increased protein extravasation and incidences of HT.…”

Mild Intraischemic Hypothermia Reduces Postischemic Hyperperfusion, Delayed Postischemic Hypoperfusion, Blood-Brain Barrier Disruption, Brain Edema, and Neuronal Damage Volume after Temporary Focal Cerebral Ischemia in Rats

“…Increased BBB permeability is closely associated with postischemic hyperperfusion in hypercapnia (Fujiwara et al, 1981), hypertension (Johansson and Linder, 1981;Kuroiwa et al, 1985a;Hatashita et al, 1986), and focal ischemia (Tamura et al, 1980). Preventing hyperperfu sion inhibits both BBB opening and brain edema (Ting et al, 1986;Seida et al, 1988;Kuroiwa et al, 1989).…”